This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the proposed studies I will investigate the hypothesis that the Francisella Pathogenicity Island encodes proteins that are secreted during infection and influence the infection process as secreted effector proteins. Francisella, a facultative intracellular pathogen that is listed as a potential agent of bioterrorism, carries a region in its genome that is crucial for intracellular growth and virulence. Some proteins encoded in this region of the Francisella Pathogenicity Island (FPI) have homologies to parts of a Type Six Secretion System (TSSS). I hypothesize that the FPI does not only encode secretion machinery but also secreted effector proteins of this TSSS. I will test this hypothesis by screening for potentially secreted proteins and describe the temporal and spatial regulation of these factors in the host cell. In addition I will test if these factors are involved in the described immune regulatory ability of Francisella.